The ultimate objective of the proposed investigation is to elucidate the mechanism by which the "non-cytopathogenic" lactic dehydrogenase-elevating virus (LDV) and the cytocidal mengovirus infect and replicate in mammalian cells and how virus replication operates within the framework of the regulatory processes of the host cells. Mengovirus replication is studied in suspension cultures of Novikoff rat hepatoma cells and LDV replication in mice and macrophage cultures. The question of how LDV affects the cellular and humoral immune systems and blood enzyme clearance of the host, and enhances tumor induction by RNA tumor viruses will be investigated by studying the replication of LDV and Friend murine leukemia virus (F-MLV) in B and T lymphocytes and in macrophage cultures. Antibodies prepared to LDV in other experimental animals and also isolated from chronically infected mice will be used to develop a method for the titration of LDV and to detect LDV replication in individual cells in culture or in tissues removed from infected animals. The mechanism of synthesis of LDV and mengovirus RNA will be studied in actinomycin-treated cultures. Attempts will be continued to isolate the mengovirus-induced RNA polymerase in a soluble form free of template RNA and to identify the enzyme responsible for the synthesis of LDV RNA. In other studies the mechanism of synthesis of the poly A segment of mengovirus RNA and its potential significance in viral RNA translation will be studied. With the use of highly purified virus, the processes involved in the adsorption and uncoating of mengovirus and the subsequent fate of the viral RNA will be investigated. Other studies will be initiated to determine the effect of LDV on host macromolecular synthesis and to elucidate the mechanism by which the synthesis of cellular RNA and protein is suppressed as a result of mengovirus infection.